Abstract Summary The overarching goal of this proposed study is to leverage existing and de novo collected data to examine the role of gender identity stigma and sexual behavior stigma on mental, sexual, and reproductive health, resilience, and access to care among transgender women. These proposed aims represent an ambitious research agenda that allows for the validation of gender-identity stigma metrics, comparison of key outcomes between transgender women and cisgender MSM, and insights into a larger and appropriately scaled online survey of transgender women with self-collection of biospecimens. Studies have consistently documented a high prevalence of adverse health outcomes among transgender women, including sexually transmitted infections, depression, and substance use. However, our understanding of the specific needs of transgender women in many parts of the world is just emerging. Work by this investigative team has included observations of higher burdens of stigma, mental health, and HIV-related outcomes as well as lower levels of resilience among transgender women when compared to cisgender MSM in settings around the world. However, there remains limited consensus on pathways determinants driving these disparities, including modifiable pathways, to improve mental health, well-being, resilience, sexual health, and access to health services among transgender women. We posit that intersectional stigmas play a major role and in response, the proposed study aims to: 1) Enroll 400 transgender women to complete an online, structured survey, including 50 that will submit self-collected biospecimen samples for biovalidation; 2) Validate gender identity stigma metrics for transgender women and characterize associations with mental health, resilience, access to care, and sexual health; and 3) Assess the feasibility of self-collection of biospecimens among a sample of transgender women sampled online. We further intend to use the results of these aims to apply for an R01 focused on a statistically powered population-based survey of transgender women in the US with self-collection of biospecimens to answer fundamentally important questions on reasons driving inequalities in health outcomes and to provide insights into appropriate interventions to address these disparities. While this is an ambitious research agenda, the investigators here represent the right team to be successful in this work with experience in stigma, gender minority research, online data collection, and psychometric analytic approaches.